Self-Stimulated Photodynamic Nanoreactor in Combination with CXCR4 Antagonists for Antileukemia Therapy.

The treatment of acute myeloid leukemia (AML) remains unsatisfactory, owing to the absence of efficacious therapy regimens over decades. However, advances in molecular biology, including inhibiting the CXCR4/CXCL12 biological axis, have introduced novel therapeutic options for AML. Additionally, self-stimulated phototherapy can solve the poor light penetration from external sources, and it will overcome the limitation that traditional phototherapy cannot be applied to the treatment of AML. Herein, we designed and manufactured a self-stimulated photodynamic nanoreactor to enhance antileukemia efficacy and suppress leukemia recurrence and metastasis in AML mouse models. To fulfill our design, we utilized the CXCR4/CXCL12 biological axis and biomimetic cell membranes in conjunction with self-stimulated phototherapy. This nanoreactor possesses the capability to migrate into the bone marrow cavity, inhibit AML cells from infiltrating into the visceral organ, significantly enhance the antileukemia effect, and prolong the survival time of leukemic mice. Therefore, this nanoreactor has significant potential for achieving high success rates and low recurrence rates in leukemia treatment.

Multifunctional agents based on 3-dicycanovinylindan-1-one acceptor: Molecular design and phototheranostic application.

Phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), has garnered considerable attention in recent years, owing to its precise spatiotemporal accuracy with minimal side effects. Recent research reveals that the combination of PDT and PTT exhibits a remarkable anti-tumor efficacy compared to PDT or PTT alone, which has put forward the new requirements of multifunctional phototherapy agents with both high photosensitization and photothermal conversion efficiencies. Among the newly developed multifunctional agents, the ones with one or two 3-dicycanovinylindan-1-one (IC) moieties as the acceptors attract much more attention, due to their long-wavelength excitation and emission, as well as high phototherapy efficacies. Therefore, in this review, the latest advancement of multifunctional agents based on IC acceptor is summarized. Especially, we focus on the structure-property relationships of the agents, as well as their biomedical application in anti-tumor therapy or image-guided therapy. Our perspective on the further future development of this field is also discussed to conclude.

Tumor Microenvironment-Triggered Self-Adaptive Polymeric Photosensitizers for Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT) employs photosensitizers to convert nearby oxygen into toxic singlet oxygen (1O2) upon laser light irradiation, showing great potential as a noninvasive approach for tumor ablation. However, the therapeutic efficacy of PDT is essentially impeded by π-π stacking and the aggregation of photosensitizers. Herein, we propose a tumor microenvironment-triggered self-adaptive nanoplatform to weaken the aggregation of photosensitizers by selenium-based oxidation at the tumor site. The selenide units in a selenium-based porphyrin-containing amphiphilic copolymer (PSe) could be oxidized into hydrophilic selenoxide units, leading to the nanoplatform self-expansion and stretching of the distance between intramolecular porphyrin units. This process could provide a better switch to greatly reduce the aggregation of photosensitive porphyrin units, generating more 1O2 upon laser irradiation. As verified in a series of in vitro and in vivo studies, PSe could be efficiently self-adapted at tumor sites, thus significantly enhancing the PDT therapeutic effect against solid tumors and minimizing side effects.

Ligand Regulation Strategy to Modulate ROS Nature in a Rhodamine-Iridium(III) Hybrid System for Phototherapy.

The efficacy of photodynamic therapy (PDT) is highly dependent on the photosensitizer features. The reactive oxygen species (ROS) generated by photosensitizers is proven to be associated with immunotherapy by triggering immunogenic cell death (ICD) as well. In this work, we establish a rhodamine-iridium(III) hybrid model functioning as a photosensitizer to comprehensively understand its performance and potential applications in photodynamic immunotherapy. Especially, the correlation between the ROS generation efficiency and the energy level of the Ir(III)-based excited state (T1'), modulated by the cyclometalating (C∧N) ligand, is systematically investigated and correlated. We prove that in addition to the direct population of the rhodamine triplet state (T1) formed through the intersystem crossing process with the assistance of a heavy Ir(III) metal center, the fine-tuned T1' state could act as a relay to provide an additional pathway for promoting the cascade energy transfer process that leads to enhanced ROS generation ability. Moreover, type I ROS can be effectively produced by introducing sulfur-containing thiophene units in C∧N ligands, providing a stronger M1 macrophage-activation efficiency under hypoxia to evoke in vivo antitumor immunity. Overall, our work provides a fundamental guideline for the molecular design and exploration of advanced transition-metal-based photosensitizers for biomedical applications.

Molecular engineering of a spheroid-penetrating phage nanovector for photodynamic treatment of colon cancer cells.

Photodynamic therapy (PDT) represents an emerging strategy to treat various malignancies, including colorectal cancer (CC), the third most common cancer type. This work presents an engineered M13 phage retargeted towards CC cells through pentavalent display of a disulfide-constrained peptide nonamer. The M13CC nanovector was conjugated with the photosensitizer Rose Bengal (RB), and the photodynamic anticancer effects of the resulting M13CC-RB bioconjugate were investigated on CC cells. We show that upon irradiation M13CC-RB is able to impair CC cell viability, and that this effect depends on i) photosensitizer concentration and ii) targeting efficiency towards CC cell lines, proving the specificity of the vector compared to unmodified M13 phage. We also demonstrate that M13CC-RB enhances generation and intracellular accumulation of reactive oxygen species (ROS) triggering CC cell death. To further investigate the anticancer potential of M13CC-RB, we performed PDT experiments on 3D CC spheroids, proving, for the first time, the ability of engineered M13 phage conjugates to deeply penetrate multicellular spheroids. Moreover, significant photodynamic effects, including spheroid disruption and cytotoxicity, were readily triggered at picomolar concentrations of the phage vector. Taken together, our results promote engineered M13 phages as promising nanovector platform for targeted photosensitization, paving the way to novel adjuvant approaches to fight CC malignancies.

Combination of Molecule-Targeted Therapy and Photodynamic Therapy Using Nanoformulated Verteporfin for Effective Uveal Melanoma Treatment.

Uveal melanoma (UM) is the most common primary ocular malignancy in adults and has high mortality. Recurrence, metastasis, and therapeutic resistance are frequently observed in UM, but no beneficial systemic therapy is available, presenting an urgent need for developing effective therapeutic drugs. Verteporfin (VP) is a photosensitizer and a Yes-Associated Protein (YAP) inhibitor that has been used in clinical practice. However, VP's lack of tumor targetability, poor biocompatibility, and relatively low treatment efficacy hamper its application in UM management. Herein, we developed a biocompatible CD44-targeting hyaluronic acid nanoparticle (HANP) carrying VP (HANP/VP) to improve UM treatment efficacy. We found that HANP/VP showed a stronger inhibitory effect on cell proliferation than that of free VP in UM cells. Systemic delivery of HANP/VP led to targeted accumulation in the UM-tumor-bearing mouse model. Notably, HANP/VP mediated photodynamic therapy (PDT) significantly inhibited UM tumor growth after laser irradiation compared with no treatment or free VP treatment. Consistently, in HANP/VP treated tumors after laser irradiation, the tumor proliferation and YAP expression level were decreased, while the apoptotic tumor cell and CD8+ immune cell levels were elevated, contributing to effective tumor growth inhibition. Overall, the results of this preclinical study showed that HANP/VP is an effective nanomedicine for tumor treatment through PDT and inhibition of YAP in the UM tumor mouse model. Combining phototherapy and molecular-targeted therapy offers a promising approach for aggressive UM management.

Natural-product-based, carrier-free, noncovalent nanoparticles for tumor chemo-photodynamic combination therapy.

Cancer, with its diversity, heterogeneity, and complexity, is a significant contributor to global morbidity, disability, and mortality, highlighting the necessity for transformative treatment approaches. Photodynamic therapy (PDT) has aroused continuous interest as a viable alternative to conventional cancer treatments that encounter drug resistance. Nanotechnology has brought new advances in medicine and has shown great potential in drug delivery and cancer treatment. For precise and efficient therapeutic utilization of such a tumor therapeutic approach with high spatiotemporal selectivity and minimal invasiveness, the carrier-free noncovalent nanoparticles (NPs) based on chemo-photodynamic combination therapy is essential. Utilizing natural products as the foundation for nanodrug development offers unparalleled advantages, including exceptional pharmacological activity, easy functionalization/modification, and well biocompatibility. The natural-product-based, carrier-free, noncovalent NPs revealed excellent synergistic anticancer activity in comparison with free photosensitizers and free bioactive natural products, representing an alternative and favorable combination therapeutic avenue to improve therapeutic efficacy. Herein, a comprehensive summary of current strategies and representative application examples of carrier-free noncovalent NPs in the past decade based on natural products (such as paclitaxel, 10-hydroxycamptothecin, doxorubicin, etoposide, combretastatin A4, epigallocatechin gallate, and curcumin) for tumor chemo-photodynamic combination therapy. We highlight the insightful design and synthesis of the smart carrier-free NPs that aim to enhance PDT efficacy. Meanwhile, we discuss the future challenges and potential opportunities associated with these NPs to provide new enlightenment, spur innovative ideas, and facilitate PDT-mediated clinical transformation.

Nanoassemblies of heptamethine cyanine dye-initiated poly(amino acid) enhance ROS generation for effective antitumour phototherapy.

Phototherapy shows great potential for pinpoint tumour treatment. Heptamethine cyanine dyes like IR783 have high potential as agents for antitumour phototherapy due to their inherent tumour targeting ability, though their effectiveness in vivo is unsatisfactory for clinical translation. To overcome this limitation, we present an innovative strategy involving IR783-based polymeric nanoassemblies that improve the dye's performance as an antitumoural photosensitizer. In the formulation, IR783 is modified with cysteamine and used to initiate the ring-opening polymerization (ROP) of the N-carboxyanhydride of benzyl-L-aspartate (BLA), resulting in IR783-installed poly(BLA). Compared to free IR783, the IR783 dye in the polymer adopts a twisted molecular conformation and tuned electron orbital distribution, remarkably enhancing its optical properties. In aqueous environments, the polymers spontaneously assemble into nanostructures with 60 nm diameter, showcasing surface-exposed IR783 dyes that function as ligands for cancer cell and mitochondria targeting. Moreover, the nanoassemblies stabilized the dyes and enhanced the generation of reactive oxygen species (ROS) upon laser irradiation. Thus, in murine tumor models, a single injection of the nanoassemblies with laser irradiation significantly inhibits tumour growth with no detectable off-target toxicity. These findings highlight the potential for improving the performance of heptamethine cyanine dyes in antitumor phototherapy through nano-enabled strategies.

Oxygen-supplemented and topography-guided epithelium-on corneal crosslinking with pulsed irradiation for progressive keratoconus.

PURPOSE: To investigate the effects of customized topography-guided epithelium-on crosslinking (epi-on CXL) with oxygen supplementation on procedural efficacy and corrected distance visual acuity (CDVA) in patients with progressive keratoconus (KC) at 1 year. SETTING: Private eye clinic, Brisbane, Australia. DESIGN: Retrospective, single-center, nonrandomized case series. METHODS: Topography-guided epi-on CXL using the Mosaic system was performed on patients with progressive KC. Oxygen goggles; transepithelial riboflavin; and pulsed, high UV-A irradiance (1 second on, 1 second off; 30 mW/cm2) were applied to enhance oxygen kinetics and bioavailabilities of riboflavin and UV-A. Guided by baseline topography, a higher UV-A dose (15 J/cm2) was applied to the area of steepest anterior curvature with decreasing fluence (as low as 7.2 J/cm2) toward the outer 9 mm. Postoperative CDVA and maximum keratometry (Kmax) were evaluated. RESULTS: 102 eyes (80 patients) were followed for 11.5 ± 4.8 months. At the latest follow-up, mean CDVA (logMAR), mean K, and Kmax (diopters [D]) improved from 0.18 ± 0.28, 46.2 ± 3.8, and 53.0 ± 5.67 at baseline to 0.07 ± 0.18, 45.8 ± 3.7, and 51.9 ± 5.56, respectively (P < .001). 3 eyes (3%) lost more than 1 CDVA line, and another 3 eyes (3%) had increased Kmax greater than 2 D. 43 eyes were followed for at least 12 months (n = 43): mean CDVA, mean K, and Kmax improved from 0.19 ± 0.33 logMAR, 46.5 ± 3.5 D, and 53.6 ± 5.67 D to 0.07 ± 0.17 logMAR, 46.0 ± 3.5 D, and 52.33 ± 5.49 D, respectively (P ≤ .002). No complications were observed. CONCLUSIONS: Tailoring oxygen-supplemented epi-on CXL with differential UV-A energy distributions, guided by baseline topography, in patients with KC seems to be safe and effective. At 1 year, study reports sustained improved CDVA and corneal stabilization.

Oxygen self-supplying small size magnetic nanoenzymes for synergistic photodynamic and catalytic therapy of breast cancer.

In recent years, tumor catalytic therapy based on nanozymes has attracted widespread attention. However, its application is limited by the tumor hypoxic microenvironment (TME). In this study, we developed oxygen-supplying magnetic bead nanozymes that integrate hemoglobin and encapsulate the photosensitizer curcumin, demonstrating reactive oxygen species (ROS)-induced synergistic breast cancer therapy. Fe3O4 magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe3O4 magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe3O4-Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe3O4-Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe3O4-Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen (1O2), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O2 carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe3O4 magnetic beads and inflicting lethal damage to cancer cells, effectively inhibiting tumor growth. Therefore, significant in vivo synergistic therapeutic effects can be achieved through catalytic-photodynamic combination therapy.

Molecular effects of photodynamic therapy with curcumin on Leishmania major promastigotes.

Leishmaniasis is a neglected disease mainly affecting low-income populations. Conventional treatment involves several side effects, is expensive, and, in addition, protozoa can develop resistance. Photodynamic therapy (PDT) is a promising alternative in treating the disease. PDT involves applying light at a specific wavelength to activate a photosensitive compound (photosensitizer, PS), to produce reactive oxygen species (ROS). Curcumin and its photochemical characteristics make it a good candidate for photodynamic therapy. Studies evaluating gene expression can help to understand the molecular events involved in the cell death caused by PDT. In the present study, RNA was extracted from promastigotes from the control and treated groups after applying PDT. RT-qPCR was performed to verify the expression of the putative ATPase beta subunit (ATPS), ATP synthase subunit A (F0F1), argininosuccinate synthase 1 (ASS), ATP-binding cassette subfamily G member 2 (ABCG2), glycoprotein 63 (GP63), superoxide dismutase (FeSODA), and glucose-6-phosphate dehydrogenase (G6PDH) genes (QR). The results suggest that PDT altered the expression of genes that participate in oxidative stress and cell death pathways, such as ATPS, FeSODA, and G6PD. The ATP-F0F1, ASS, and GP63 genes did not have their expression altered. However, it is essential to highlight that other genes may be involved in the molecular mechanisms of oxidative stress and, consequently, in the death of parasites.

Synergetic Pyroptosis with Apoptosis Improving Phototherapy of Mitochondria-Targeted Cyanines with Superior Photostability.

Pyroptosis has been reported to improve the antitumor effect by evoking a more intense immune response and a therapeutic effect. For phototherapy, several photosensitizers have been found to initiate pyroptosis. However, the effect of pyroptosis associated with apoptosis in enhancing the antitumor therapy needs sufficient characterization, especially under long-term treatment. As a NIR photosensitizer, heptamethine cyanines have been discovered for anticancer phototherapy for deep tissue penetration and inherent tumor-targeted capability. However, they are not quite stable for long-term performance. To investigate the effect of pyroptosis along with apoptosis on the anticancer immune responses and phototherapy, here, we chemically modulate the cyanine IR780 to regulate hydrophobicity, stability, and intracellular targeting. Two photosensitizers, T780T-TPP and T780T-TPP-C12, were finally optimized and showed excellent photostability with high photothermal conversion efficiency. Although the cellular uptake of the two molecules was both mediated by OATP transporters, T780T-TPP induced tumor cell death via pyroptosis and apoptosis and accumulated in tumor accumulation, while T780T-TPP-C12 was prone to accumulate in the liver. Ultimately, via one injection-multiple irradiation treatment protocol, T780T-TPP displayed a significant antitumor effect, even against the growth of large tumors (200 mm3).

Research Progress of Natural Product Photosensitizers in Photodynamic Therapy.

Photodynamic therapy is a noninvasive cancer treatment that utilizes photosensitizers to generate reactive oxygen species upon light exposure, leading to tumor cell apoptosis. Although photosensitizers have shown efficacy in clinical practice, they are associated with certain disadvantages, such as a certain degree of toxicity and limited availability. Recent studies have shown that natural product photosensitizers offer promising options due to their low toxicity and potential therapeutic effects. In this review, we provide a summary and evaluation of the current clinical photosensitizers that are commonly used and delve into the anticancer potential of natural product photosensitizers like psoralens, quinonoids, chlorophyll derivatives, curcumin, chrysophanol, doxorubicin, tetracyclines, Leguminosae extracts, and Lonicera japonica extract. The emphasis is on their phototoxicity, pharmacological benefits, and effectiveness against different types of diseases. Novel and more effective natural product photosensitizers for future clinical application are yet to be explored in further research. In conclusion, natural product photosensitizers have potential in photodynamic therapy and represent a promising area of research for cancer treatment.

Encapsulated Rose Bengal Enhances the Photodynamic Treatment of Triple-Negative Breast Cancer Cells.

Among breast cancer subtypes, triple-negative breast cancer stands out as the most aggressive, with patients facing a 40% mortality rate within the initial five years. The limited treatment options and unfavourable prognosis for triple-negative patients necessitate the development of novel therapeutic strategies. Photodynamic therapy (PDT) is an alternative treatment that can effectively target triple-negative neoplastic cells such as MDA-MB-231. In this in vitro study, we conducted a comparative analysis of the PDT killing rate of unbound Rose Bengal (RB) in solution versus RB-encapsulated chitosan nanoparticles to determine the most effective approach for inducing cytotoxicity at low laser powers (90 mW, 50 mW, 25 mW and 10 mW) and RB concentrations (50 µg/mL, 25 µg/mL, 10 µg/mL and 5 µg/mL). Intracellular singlet oxygen production and cell uptake were also determined for both treatment modalities. Dark toxicity was also assessed for normal breast cells. Despite the low laser power and concentration of nanoparticles (10 mW and 5 µg/mL), MDA-MB-231 cells experienced a substantial reduction in viability (8 ± 1%) compared to those treated with RB solution (38 ± 10%). RB nanoparticles demonstrated higher singlet oxygen production and greater uptake by cancer cells than RB solutions. Moreover, RB nanoparticles display strong cytocompatibility with normal breast cells (MCF-10A). The low activation threshold may be a crucial advantage for specifically targeting malignant cells in deep tissues.

NIR-Triggered Thermosensitive Nanoreactors for Dual-Guard Mechanism-Mediated Precise and Controllable Cancer Chemo-Phototherapy.

Thermosensitive nanoparticles can be activated by externally applying heat, either through laser irradiation or magnetic fields, to trigger the release of drug payloads. This controlled release mechanism ensures that drugs are specifically released at the tumor site, maximizing their effectiveness while minimizing systemic toxicity and adverse effects. However, its efficacy is limited by the low concentration of drugs at action sites, which is caused by no specific target to tumor sties. Herein, hyaluronic acid (HA), a gooey, slippery substance with CD44-targeting ability, was conjugated with a thermosensitive polymer poly(acrylamide-co-acrylonitrile) to produce tumor-targeting and thermosensitive polymeric nanocarrier (HA-P) with an upper critical solution temperature (UCST) at 45 °C, which further coloaded chemo-drug doxorubicin (DOX) and photosensitizer Indocyanine green (ICG) to prepare thermosensitive nanoreactors HA-P/DOX&ICG. With photosensitizer ICG acting as the "temperature control element", HA-P/DOX&ICG nanoparticles can respond to temperature changes when receiving near-infrared irradiation and realize subsequent structure depolymerization for burst drug release when the ambient temperature was above 45 °C, achieving programmable and on-demand drug release for effective antitumor therapy. Tumor inhibition rate increased from 61.8 to 95.9% after laser irradiation. Furthermore, the prepared HA-P/DOX&ICG nanoparticles possess imaging properties, with ICG acting as a probe, enabling real-time monitoring of drug distribution and therapeutic response, facilitating precise treatment evaluation. These results provide enlightenment for the design of active tumor targeting and NIR-triggered programmable and on-demand drug release of thermosensitive nanoreactors for tumor therapy.

Photoresponsive metal-organic framework with combined photodynamic therapy and hypoxia-activated chemotherapy for the targeted treatment of rheumatoid arthritis.

Activated M1-type macrophages, which produce inflammatory factors that exacerbate rheumatoid arthritis (RA), represent crucial target cells for inhibiting the disease process. In this study, we developed a novel photoresponsive targeted drug delivery system (TPNPs-HA) that can effectively deliver the hypoxia-activated prodrug tirapazamine (TPZ) specifically to activated macrophages. After administration, this metal-organic framework, PCN-224, constructed uing the photosensitizer porphyrin, exhibits the ability to generate excessive toxic reactive oxygen species (ROS) when exposed to near-infrared light. Additionally, the oxygen-consumed hypoxic environment further activates the chemotherapeutic effect of TPZ, thus creating a synergistic combination of photodynamic therapy (PDT) and hypoxia-activated chemotherapy (HaCT) to promote the elimination of activated M1-type macrophages. The results highlight the significantly potential of this photoresponsive nano-delivery system in providing substantial relief for RA. Furthermore, these findings support its effectiveness in inhibiting the disease process of RA, thereby offering new possibilities for the development of precise and accurate strategies for RA.

Near-infrared photoimmunotherapy targeting Nectin-4 in a preclinical model of bladder cancer.

Enfortumab vedotin (EV), an antibody-drug conjugate (ADC) that targets Nectin-4, has shown promising results in the treatment of bladder cancer. However, multiple resistance mechanisms that are unique to ADCs limit the therapeutic potential of EV in clinical practice. Here, we developed and tested a Nectin-4-targeted near-infrared photoimmunotherapy (NIR-PIT) that utilizes the same target as EV but utilizes a distinct cytotoxic and immunotherapeutic pathway in preclinical models of bladder cancer. NIR-PIT was effective in vitro against luminal subtype human bladder cancer cell lines (RT4, RT112, MGH-U3, SW780, and HT1376-luc), but not against other subtype cell lines (UMUC3 and T24). In vivo, the tumor site was clearly visible by Nectin-4-IR700 fluorescence 24 h after its administration, suggesting the potential as an intraoperative imaging modality. NIR-PIT significantly suppressed tumor growth and prolonged survival in SW780 and RT112 xenograft models. Weekly treatment with NIR-PIT further improved tumor control in RT112 xenograft models. The effectiveness of NIR-PIT was also confirmed in HT1376-luc orthotopic xenograft models. Histological analysis verified that NIR-PIT induced a significant pathologic response. Taken together, Nectin-4-targeted NIR-PIT shows promise as a treatment for luminal subtype bladder cancers.

Influence of photoactivation on tissue response to different dyes used in photodynamic therapy and laser ablation therapy.

Laser ablation therapy (LA) uses Indocyanine Green dye (ICG) which efficiently absorbs laser energy and the increased temperature results in an instantaneous flame that chars tissue and microbes. Photodynamic therapy (PDT) uses different dyes that are activated by light to kill bacteria. This study evaluated the biocompatibility of the dye Curcumin (CUR), Methylene Blue (MB), and Indocyanine Green (ICG) before and after laser activation (ACT). Polyethylene tubes containing one of the dyes were implanted in the subcutaneous tissue of 32 rats (4 tubes per rat) which were divided into 8 groups: C - control (saline solution); C + ACT (Red Laser 660 nm); CUR; CUR + ACT (480 nm blue LED); MB; MB + ACT (Red Laser 660 nm); ICG; ICG + ACT (810 nm Infrared Laser). After 7 and 30 days (n = 8/time), the rats were euthanized and the tubes with the surrounding tissue were removed and processed for histological analysis of inflammation using H&E stain, and collagen fiber maturation using picrosirius red (PSR). A two-way analysis of variance statistical test was applied (p < 0.05). At 7 days, regardless of laser activation, the CUR group showed a greater inflammatory infiltrate compared to the ICG and control groups, and the MB group had a greater inflammation only in relation to the control (p < 0.05). At 30 days, CUR and MB groups showed a greater inflammatory infiltrate than the control (p < 0.05). ICG group was equal to the control in both periods, regardless of the laser activation (p > 0.05). Laser activation induced the proliferation of collagen immature fibers at 7 days, regardless of the dye (p < 0.05). The CUR group showed a lower percentage of immature and mature fibers at 7 days, compared to ICG and control (p < 0.05) and, at 30 days, compared to control (p < 0.05). Regardless of laser activation, the ICG showed the results of collagen maturation closest to the control (p > 0.05). It was concluded that all dyes are biocompatible and that laser activation did not interfere with biocompatibility. In addition, the maturity of collagen was adequate before and after the laser activation. These results demonstrate that the clinical use of dyes is safe even when activated with a laser.

Ferroptosis boosted oral cancer photodynamic therapy by carrier-free Sorafenib-Ce6 self-assembly nanoparticles.

Oral cancer is a disease with high morbidity and mortality worldwide and greatly impacts the quality of life, especially in patients with advanced stages. Photodynamic therapy (PDT) is one of the most effective clinical treatments for oral cancers. However, most clinically applied photosensitizers have several deficiencies, including oxygen dependence, poor aqueous solubility, and a lack of tumor-targeting ability. Herein, the carrier-free multifunctional Sorafenib (Sor), chlorin e6 (Ce6), and Fe3+ self-assembly co-delivery nanoparticles (Sor-Ce6 NPs) were constructed via combining a ferroptosis inducer Sor and a photosensitizer Ce6 for synergetic therapy. The as-synthesized Sor-Ce6 NPs presented excellent colloidal stability and water dispersity with good in vivo tumor-targeting ability. More significantly, the low dose of Sor-Ce6 NPs had little dark toxicity but produced significantly enhanced ROS and supplied O2 sustainably to increase phototoxicity through ferroptosis pathway. Notably, the Sor-Ce6 NPs showed significantly higher in vitro and in vivo anti-tumor efficacy than the Sor/Ce6 mixture due to the improvement of cellular uptake and the incorporation of foreign Fe ions in the system, which also confer the T1 magnetic resonance-guided imaging ability to the formed Sor-Ce6 NPs. Our study demonstrates a promising self-assembled strategy for overcoming hypoxia-related PDT resistance for oral cancer treatment.

Nanomaterials-assisted photothermal therapy for breast cancer: State-of-the-art advances and future perspectives.

Breast cancer (BC) remains an enigmatic fatal modality ubiquitously prevalent in different parts of the world. Contemporary medicines face severe challenges in remediating and healing breast cancer. Due to its spatial specificity and nominal invasive therapeutic regime, photothermal therapy (PTT) has attracted much scientific attention down the lane. PTT utilizes a near-infrared (NIR) light source to irradiate the tumor target intravenously or non-invasively, which is converted into heat energy over an optical fibre. Dynamic progress in nanomaterial synthesis was achieved with specialized visual, physicochemical, biological, and pharmacological features to make up for the inadequacies and expand the horizon of PTT. Numerous nanomaterials have substantial NIR absorption and can function as efficient photothermal transducers. It is achievable to limit the wavelength range of an absorbance peak for specific nanomaterials by manipulating their synthesis, enhancing the precision and quality of PTT. Along the same lines, various nanomaterials are conjugated with a wide range of surface-modifying chemicals, including polymers and antibodies, which may modify the persistence of the nanomaterial and diminish toxicity concerns. In this article, we tend to put forth specific insights and fundamental conceptualizations on pre-existing PTT and its advances upon conjugation with different biocompatible nanomaterials working in synergy to combat breast cancer, encompassing several strategies like immunotherapy, chemotherapy, photodynamic therapy, and radiotherapy coupled with PTT. Additionally, the role or mechanisms of nanoparticles, as well as possible alternatives to PTT, are summarized as a distinctive integral aspect in this article.